Beta-Blockers Therapy for the Treatment of Hypertension
Beta-blockers should not be recommended as first-line therapy for hypertension in patients without heart disease, according to a new study. Researchers from Sweden performed a meta-analysis on 13 randomized controlled trials comparing treatment with beta-blockers with other antihypertensive drugs. Seven other studies were reviewed in which beta-blockers were compared with placebo or no treatment. The relative risk of stroke was 16% higher for patients who were treated with beta-blockers (95% CI, 4-30%) compared to other drugs. Beta-blockers reduced the relative risk of stroke by 19% compared to no treatment or placebo; however, this was about half the reduction expected from previous hypertension trials. There was no difference seen in the rates of myocardial infarction or overall mortality. A possible mechanism for these findings is that beta-blockers reduce brachial blood pressure out of proportion to central blood pressure compared with other antihypertensives.
The authors suggest that beta-blockers are less effective than other antihypertensive drugs in preventing stroke, and should not be a first choice in the treatment of primary hypertension (Lindholm LH, et al. Should Beta Blockers Remain First Choice in the Treatment of Primary Hypertension? A Meta-Analysis. Lancet. 2005;366:1545-1553). This same group published a study in 2004, suggesting that atenalol was a poor choice for treatment of hypertension (Carlberg B, et al. Atenolol in Hypertension: Is It Wise?Lancet. 2004;364:1684-1689). An accompanying editorial states "Surely, therefore, the era of beta-blockers for hypertension is over," but suggests that these drugs should not be discontinued abruptly, and should be discontinued with extreme caution in patients with coronary artery disease (Beever DG, et al. The End of Beta Blockers for Uncomplicated Hypertension? Lancet. 2005;366:1510-1512).
Treatments for Acute Migraine
Two studies in the September issue of the Journal of Headache find that sumatriptan alone is inferior to other treatments for acute migraine. In the first study, 972 migraine patients were randomized to treatment with sumatriptan 50 mg, naproxen sodium 500 mg, sumatriptan 50 mg plus naproxen 500 mg, or placebo at the onset of headache symptoms. The sumatriptan plus naproxen group fared the best, with 46% of subjects achieving a 24-hour pain relief response. Sumatriptan alone resulted in 29% of patients achieving the same result, while naproxen alone resulted in the 25% response, and placebo resulted in a 17% response (P < .001). Relief of pain at 2 hours was achieved in 65% of the combination group, 49% of the sumatriptan patients, 46% of naproxen patients, and 27% of placebo patients (P < .001). The incidence of recurrent headache 24 hours later was also lowest in the sumatriptan plus naproxen group. Other migraine symptoms, including nausea, photophobia, and phonophobia were also most effectively treated with sumatriptan plus naproxen. Adverse effects were similar in all the treatment groups (Smith TR, et al. Sumatriptan and Naproxen Sodium for the Acute Treatment of Migraine. Headache. 2005;45:983-991). In the second study, sumatriptan was compared with acetaminophen-aspirin-caffeine (AAC) in the early treatment of migraine. In a randomized, controlled clinical trial, 171 patients took either sumatriptan 50 mg or AAC (acetaminophen 500 mg, aspirin 500 mg, and caffeine 130 mg [Excedrin Extract Strength 2 tabs], or Excedrin Migraine 2 tabs at the first sign of a migraine attack. AAC was significantly more effective (P > .05) than sumatriptan in the early treatment of migraine, as shown by superiority and summed pain intensity difference, pain relief, pain intensity difference, response, sustained response, relief of assisted symptoms, use of rescue medications, disability relief, and global assessments of effectiveness (Goldstein J, et al. Acetaminophen, Aspirin, and Caffeine Versus Sumatriptan Succinate in the Early Treatment of Migraine: Results From the ASSET Trial. Headache. 2005;45:973-982).
Statin Therapy for ACS Patients
Early aggressive statin therapy is beneficial for patients with acute coronary syndrome (ACS), according to a new study. In a continuation of the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT -TIMI 22) trial, the timing of intensive statin therapy was evaluated in patients with acute coronary syndrome. A total of 4162 patients with ACS were randomized to intensive statin therapy with atorvastatin 80 mg or standard therapy with pravastatin 40 mg. The composite end points of death, MI, or rehospitalization for recurrent ACS were determined for each group at 30 days. ACS patients who were started in the hospital on intensive statin therapy fared better than those with standard therapy (composite end point at 30 days 3% intensive therapy vs 4.2% standard therapy [HR = 0 .72; 95% CI, 0.52 to 0.99; P = .046]). The authors conclude that ACS patients should be started on aggressive statin therapy in the hospital and continued long-term (Ray KK, et al. Early and Late Benefits of High-Dose Atorvastatin in Patients With Acute Coronary Syndromes: Results from the PROVE IT-TIMI 22 Trial. J Am Coll Cardiol. 2005;46:1405-1410). In another follow-up from the PROVE IT-TIMI 22 study in the same Journal, researchers looked at whether very low LDL levels from aggressive statin therapy are associated with adverse effects. Thirty-one percent of patients treated with atorvastatin achieved LDL levels between 80 and 60mg/dL, with another 34% between 60 and 40 mg/dL, and 11% less than 40 mg/dL. There were no significant differences in safety parameters, including muscle, liver, or retinal abnormalities, intracranial hemorrhage, or death in the very low LDL groups. Patients with LDL levels less than 60 had fewer major cardiac events, including death MI and stroke. The authors conclude that very low LDL levels are not associated with adverse effects, and appear to be associated with fewer adverse cardiovascular outcomes (Wiviott SD, et al. Can Low-Density Lipoprotein Be Too Low? The Safety and Efficacy of Achieving Very Low Low-Density Lipoprotein With Intensive Statin Therapy: A PROVE IT-TIMI 22 Substudy. J Am Coll Cardiol. 2005;46:1411-1416).
The Correct Dosing for Onychomycosis
Many physicians have prescribed terbinafine in a pulse-dosing regimen of 2 pills per day for one week, one week a month, for 3 to 4 months for the treatment of onychomycosis. The regimen is thought to increase compliance, as well as reduce cost. Pulse dosing however is not an approved therapy, and now a new study suggests that it is not as effective as once daily dosing.
The study recruited 306 volunteers with onychomycosis, involving at least 25% of the toenail. Patients were randomized to terbinafine 250 mg daily for 3 months or terbinafine 500 mg daily for one week per month for 3 months. Mycological cures were higher with once-a-day dosing (71% vs 58.7%; P = .03). Clinical cures were also higher with once-a-day dosing (44.6% vs 29.4%; P = .007), as were complete cures of target toenail (40.5% vs 28.0%; P = .02), and complete cure of all 10 toenails (25.2% vs 14.7%; P = .03). Tolerability of the regimens did not differ significantly between groups.
The authors conclude that once daily dosing appears to be superior to pulse dosing, however, they also found "this expensive therapy to me much less effective than previously believed, particular for achieving complete cure of all 10 toenails" (Warshaw EM, et al. Pulse Versus Continuous Terbinafine for Onychomycosis: A Randomized, Double-Blind, Controlled Trial. J Am Acad Dermatol. 2005;53:578-584).
The FDA has approved the once-a-day oral iron chelator for the treatment of chronic iron overload due to blood transfusions. Novartis will market deferasirox (Exjade) as an oral alternative to intravenous chelating agents.
This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: [email protected].Beta-Blockers Therapy for the Treatment of Hypertension; Treatments for Acute Migraine; Statin Therapy for ACS Patients; The Correct Dosing for Onychomycosis; FDA Actions
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